Abnormalities in autonomic control in sickle cell anemia (SCA) patients have been reported by multiple researchers. However their potential causal association with sickle cell crisis remains unknown. We employed hypoxia, a known trigger to sickle cell crisis, to perturb the autonomic systems of the subjects. Cardiac autonomic control was non-invasively assessed by tracking the changes in heart rate variability (HRV) that occur following brief exposure to a hypoxia stimulus. Time varying spectral analysis of HRV was applied to estimate the cardiac autonomic response to the transient episode of hypoxia. The results demonstrate that cardiovascular autonomic response to hypoxia is substantially more sensitive in SCA than in normal controls. We also developed a model to compensate for the confounding effects of respiration on the HRV spectral indices by using the corresponding respiration signal to compensate for the respiratory correlated part of the HRV. This technique improved the resolution with which the effect of hypoxia on changes in HRV could be measured.